A facile and efficient synthesis of benzimidazole as potential anticancer agents

This study reports a simple process to synthesize and separate of 2-(substituted-phenyl) benzimidazole derivatives with high yield and efficiency. Specifically, by reacting ortho-phenylenediamines with benzaldehydes using sodium metabisulphite as an oxidation agent in a mixture of solvent under mild condition, twenty-three compounds of benzimidazoles were obtained and separated easily using hexane and water to wash, respectively. The structure of all obtained compounds was identified by FTIR, NMR and HRMS. The SAR analysis of synthesized benzimidazoles on human lung (A549), breast (MDA-MB-231) and prostate (PC3) cancer cell lines showed that the presence of methyl group at 5(6)-position on benzimidazole scaffold was a contributing factor influencing the anticancer activity. The presence of electron-donating groups (OH, OMe, –NMe 2 , –O–CH 2 –C 6 H 5 ) also caused significant increase of anticancer activity, while the presence of electron-withdrawing groups (–NO 2 , –CF 3 ) on the phenyl group at 2-position of benzimidazole ring decreased the ability of inhibition of synthesized benzimidazoles. The compounds 2f and 2g displayed the significant anticancer activity on both A549 and PC3 cell lines. Graphic abstract Two series of 2-phenylbenzimidazoles were synthesized by simple process with high yield and efficiency and they were illumiated the effect of substituent groups in their structures on the bioactivity against three cancer cell line A549, MDA-MB-231 and PC3.